This is an application to support a career development program for Dr. Olivia Okereke; the proposed project will facilitate her establishment as an independent investigator in the epidemiology of cognitive decline. The research plan will focus on how key factors strongly associated with cardiovascular disease risk - dietary fat composition and plasma lipids - relate to cognitive decline in older participants of the Women's Health Study (WHS). Furthermore, in order to address the candidate's hypotheses regarding mechanistic links between dietary fats and cognitive change, she proposes new collection of two innovative markers of oxidative stress among a subset of participants: plasma oxidized LDL and fluorescent oxidation products. First, Dr. Okereke will examine whether elevated consumption of saturated and trans-unsaturated fats is related to increased cognitive decline over five years of follow-up. Second, she will evaluate whether higher intake of mono- and polyunsaturated fatty acids are associated with decreased cognitive decline; she will also evaluate whether higher fish consumption and greater adherence to Mediterranean diet are associated with less cognitive decline. Third, she will assess the relation of plasma LDL and HDL to cognitive decline, as well as the interactions between dietary fats and plasma lipids on paths of cognitive change. Finally, she will examine whether higher levels of novel plasma markers of oxidative stress are related to increased cognitive decline, and explore mediation by oxidative stress of associations between dietary fat and cognitive change. Dr. Okereke will utilize prospectively collected data from the WHS cognitive study, which includes 6,000+ female participants with 3 repeated cognitive assessments, and will analyze data using modern statistical techniques of mixed-effects models of cognitive change. By addressing potentially modifiable risk factors for cognitive decline, this project will yield information of great public health importance for older Americans. Central to this application is the comprehensive training plan. Dr. Okereke will gain experience with key epidemiologic research tools, including methods for longitudinal analysis, dietary and cognitive assessment, and blood/biomarker data collection, all within a supportive institutional environment. Formal coursework, research group meetings, and individual mentoring will supplement her learning. Overall, this proposal will ensure that Dr. Okereke is poised to become a leading investigator in the area of cognitive function. [unreadable] [unreadable] [unreadable]